The present invention is directed to novel vinyl sulfenic acid derivatives, useful for the synthesis of benzo b!thiophenes, in particular 2-arylbenzo b!thiophenes.
Benzo b!thiophenes have been prepared by a number of different synthetic routes. One of the most widely used methods is the oxidative cyclization of o-mercaptocinnamic acids. This route is limited to the preparation of benzo b!thiophene-2-carboxylates. 2-Phenylbenzo b!thiophenes are prepared by acid-catalyzed cyclization of 2-phenylthioacetaldehyde dialkyl acetals. Unsubstituted benzo b!thiophenes are prepared by catalytic condensation of styrene and sulfur. 3-Substituted benzo b!thiophenes are prepared by acid-catalyzed cyclization of arylthiomethyl ketones; however, this route is limited to the preparation of 3-alkylbenzo b!thiophenes. See Campaigne, "Thiophenes and their Benzo Derivatives: (iii) Synthesis and Applications," in Comprehensive Heterocyclic Chemistry (Katritzky and Rees, eds.), Volume IV, Part III, 863-934 (1984). 3-Chloro-2-phenylbenzo b!thiophene is prepared by the reaction of diphenylacetylene with sulfur dichloride. Barton and Zika, J. Org. Chem., 35, 1729-1733 (1970). Benzo b!thiophenes have also been prepared by pyrolysis of styryl sulfoxides. However, low yields and extremely high temperatures make this route unsuitable for production-scale syntheses. See Ando, J. Chem. Soc., Chem. Comm., 704-705 (1975).
Sulfenic acids have been postulated as key intermediates in a variety of chemical reactions; however, very few examples exist of the isolation of these compounds. See Shelton and Davis, J. Am. Chem. Soc., 89(3), 718-719 (1968) and Davis et al., J. Am. Chem. Soc., 100, 2844 (1978). Sulfenic acids have been generated in situ, and intramolecularly or intermolecularly cyclyzed with olefins and acetylenes. See Mazzanti et al., J. Chem. Soc., Perkin Trans. I, 3299-3004 (1944) and Davis et al., J. Org. Chem., 45, 1650-1653 (1980). A series of trimethylsilyl arenesulfenates have been prepared from the corresponding N-benzylidenearenesulfinamides; however, the yield of the trimethylsilyl ester was generally very low. Davis et al., J. Org. Chem., 45, 1650-1653 (1980).
The preparation of 6-hydroxy-2-(4-hydroxyphenyl)benzo b!thiophenes was described in U.S. Pat. Nos. 4,133,814 and 4,380,635. One process described in these patents is the acid-catalyzed intramolecular cyclization/rearrangement of .alpha.-(3-methoxyphenylthio)-4-methoxyacetophenone. The reaction of this starting compound in neat polyphosphoric acid at about 85.degree. C. to about 90.degree. C. gives an approximate 3:1 mixture of two regioisomeric products: 6-methoxy-2-(4-methoxyphenyl)benzo b!thiophene and 4-methoxy-2-(4-methoxyphenyl)benzo b!thiophene. These isomeric benzo b!thiophenes co-precipitate from the reaction mixture, producing a mixture containing both compounds. To obtain a single regioisomer, the regioisomers must be separated, such as by chromatography or fractional crystallization. Therefore, there currently exists a need for an efficient and regiospecific synthesis of 2-arylbenzo b!thiophenes from readily available starting materials.